PMID- 24488323
OWN - NLM
STAT- MEDLINE
DCOM- 20140715
LR  - 20221207
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 73
IP  - 4
DP  - 2014 Apr
TI  - Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in 
      Japanese patients with castration-resistant prostate cancer.
PG  - 703-10
LID - 10.1007/s00280-014-2394-z [doi]
AB  - PURPOSE: The purpose of the study is to analyze the pharmacokinetic (PK) profile 
      of cabazitaxel and evaluate its safety and tolerability as a 1-h IV infusion 
      every 3 weeks in Japanese patients with castration-resistant prostate cancer 
      (CRPC). METHODS: Seventeen patients were treated with cabazitaxel at doses of 20 
      and 25 mg/m(2) for PK analyses. Dose escalation was performed only in the absence 
      of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was the highest 
      dose at which less than 33 % of the patients developed DLT. RESULTS: Cabazitaxel 
      exhibited a triphasic elimination profile with a long terminal half-life of 116 +/- 
      29.0 or 113 +/- 28.0 h after IV infusion of 20 or 25 mg/m(2) cabazitaxel, 
      respectively. The major differences in the PK parameters of cabazitaxel and 
      docetaxel were cabazitaxel's fairly high clearance rate, representing 
      approximately half the hepatic flow, and its large volume of distribution at 
      steady-state conditions. No DLT was observed during Cycle 1. Mild-to-moderate 
      hematological adverse events (AEs), including neutropenia, and other AEs 
      typically associated with taxanes were observed; all AEs were manageable. 
      Cabazitaxel at 25 mg/m(2) every 3 weeks was selected as the MTD in Japanese 
      patients. CONCLUSIONS: The PK parameters of cabazitaxel in Japanese CRPC patients 
      were comparable with those previously determined in Caucasian subjects. The 
      safety and tolerability of cabazitaxel were also comparable in both ethnic 
      populations.
FAU - Mukai, Hirofumi
AU  - Mukai H
AD  - National Cancer Center Hospital East, 6-5-1 Kashiwanoha Kashiwa-Shi, Chiba, 
      277-8577, Japan, hrmukai@east.ncc.go.jp.
FAU - Takahashi, Shunji
AU  - Takahashi S
FAU - Nozawa, Masahiro
AU  - Nozawa M
FAU - Onozawa, Yusuke
AU  - Onozawa Y
FAU - Miyazaki, Jun
AU  - Miyazaki J
FAU - Ohno, Keiji
AU  - Ohno K
FAU - Suzuki, Kazuhiro
AU  - Suzuki K
CN  - TED 11576 investigators
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140201
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Taxoids)
RN  - 51F690397J (cabazitaxel)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Asian People
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Prostatic Neoplasms, Castration-Resistant/*drug therapy/*metabolism/pathology
MH  - Taxoids/*administration & dosage/adverse effects/*pharmacokinetics
EDAT- 2014/02/04 06:00
MHDA- 2014/07/16 06:00
CRDT- 2014/02/04 06:00
PHST- 2013/12/27 00:00 [received]
PHST- 2014/01/16 00:00 [accepted]
PHST- 2014/02/04 06:00 [entrez]
PHST- 2014/02/04 06:00 [pubmed]
PHST- 2014/07/16 06:00 [medline]
AID - 10.1007/s00280-014-2394-z [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2014 Apr;73(4):703-10. doi: 
      10.1007/s00280-014-2394-z. Epub 2014 Feb 1.